Registration Dossier

Administrative data

Description of key information

Irritation studies for skin and eye were conducted according to Draize method in rabbits with a test item containing 63-67% active ingredient. Scoring according to Draize demonstrated  mean 24-72h scores of 2/4 and 1.1/4 for skin erythema and edema, respectively. For the eye, mean 24-72h scores were 1.4/4 for cornea, 1/2 for iris, 3/3 for conjuctiva and 2.6/4 for chemosis. Changes were still observed after the 72h period, but were reversible within 14 days. Based on the scores, the substance was considered irritating for skin (CLP category 2) and, in combination with various eye findings which were not reversible, causing severe eye damage (CLP category 1).

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a key study for skin irritation, three New Zealand White rabbits were treated with registered substance under occlusion with 0.5 mL containing 63 -67% active ingredient of the test item on the skin for 24 hours (Kreiling and Jung, 1988a). Observations were performed 30-60 minutes and 24, 48 and 72 hours after removal of the patch. Mean 24 -72h scores were 2/4 for erythema and 1.1/4 for edema. At 72 hours there were still findings, thus additional observations were done at 7, 14 and 21 days after patch removal. One to 48 hours after removal of the patch, the animals showed barely perceptible to clearly defined erythema and partially very slight to slight edema . 72 hours after application partially clearly defined to moderate erythema and very slight edema were observed. In one animal the reddening was not assessable due to discoloration. 7 days after application no irritation was observed. 14 to 21 days after application, one animal showed barely perceptible to moderate erythema. The irritations 24 hours to 14 days after patch removal partially included dry, brittle, fine or large flaking and parchment-like skin surface, fissured skin, induration, eschar formation and large-area yellow or light-brown skin discoloration.

In conclusion, irritation was observed with the 63-67% formulation and no data were available for higher concentrations, nevertheless there were no hints for corrsosion and the findings were generally reversible, therefore skin irritation Categgory 2 is also assumed for the neat substance.

 

Eye irritation

In a key study for eye irritation, three New Zealand rabbits underwent a single application of the registered substance in the conjunctival sac of the left eye of 0.1 mL containing 63 -67% active ingredient of the test item (Kreiling and Jung, 1988b). The untreated eye served as a control. 24 Hours after administration of the test item as well as to all other assessment time points at which, the treated eyes still showed discharges or in which a corneal examination with fluorescein sodium solution was done, the treated eyes were thoroughly washed with physiological saline solution (ca. 37°C). Mean 24 -72h scores were 1.4/4 for cornea, 1/2 for iris, 3/3 for conjuctiva and 2.6/4 for chemosis. One to 72 hours after application, the conjunctivae showed a diffuse bright red color and a very clear swelling to a swelling with more than half-closed lids. The iris was red, the cornea showed diffuse opacity areas to easily discernible translucent areas. 7 Days after application significant hyperemia of some blood vessels to diffuse crimson-red colored conjunctivae and very slightly to significantly swollen conjunctivae were observed. One animal showed scattered areas of opacity of the cornea. 14 Days after application all signs of irritation were reversible. One hour to 7 days after application, the irritation was accompanied with a clear, colorless or white mucous discharge. One animal showed 24 hours to 7 days after application partially white discolorations, bleeding and detachments of parts of the conjunctivae and nictitating membrane.

In conclusion, moderate eye scores were observed during the 72h period, followed by additional observations during the recovery period, including opacity in one animal. Allthough all signs of irritation were reversible, a worst case Category 1 is assumed for the registered substance, which complies with the Categroy 1 group classification for eye damage for the di-ester sulfosuccinates.

 

Conclusion

- The substance tested for skin irritation containing 63 -67 % active ingredient was concluded to be irritating for skin (CLP Category 2) and causing severe eye damage (CLP Category 1). As the skin findings were generally reversible and there were no hints for corrsosion, skin irritation Categgory 2 can also be assumed for the neat substance.

-Further information supporting the classification is provided in the read across justification for the Di-ester category, showing that all substances in the group were group classified to cause skin irritation (CLP category 2) and severe eye damage (CLP category 1).


Justification for selection of skin irritation / corrosion endpoint:
Key study

Justification for selection of eye irritation endpoint:
Key study

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on the results the test substance needs to be classified for skin irritation according to the Directive 67/548/EEC, Annex VI with symbol Xi and the indication of danger “irritant”; the following risk phrase shall be assigned: R38 - Irritating to skin.  For the eye, it is classified as irritating to eyes and risk phrase R41- Risk of serious damage to eyes shall be assigned.

According to CLP regulation (No. 1272/2008 of 16 December 2008), the substance is classified as Category 2, with signal word 'Warning' and hazard statement: H315 - Causes skin irritation. For the eye, Category 1, with signal word 'Danger' and hazard statement: H319 -Causes serious eye damage is proposed.